Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20–365 from study allocation and (ii) days alive and without exacerbation within days 20–365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142. Registered on August 25, 2017. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06720-z

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Additional file 4 of On Jones et al.’s method for extending Bland-Altman plots to limits of agreement with the mean for multiple observers

Additional file 4. Formulae after removing the observer effect

Additional file 2 of On Jones et al.’s method for extending Bland-Altman plots to limits of agreement with the mean for multiple observers

Additional file 2. Coverage probabilities from a small simulation study

Additional file 1 of On Jones et al.’s method for extending Bland-Altman plots to limits of agreement with the mean for multiple observers

Additional file 1. Derivation of the confidence intervals for the LOAM

Additional file 3 of On Jones et al.’s method for extending Bland-Altman plots to limits of agreement with the mean for multiple observers

Additional file 3. Derivation of confidence intervals for the variance parameters

The majority of Danish breast cancer survivors on adjuvant endocrine therapy have clinically relevant sexual dysfunction: a cross-sectional study

Impairments in sexual function are common among breast cancer survivors (BCSs), particularly in BCSs receiving adjuvant endocrine therapy (AET). Whether these impairments cause distress, thus qualifying for a more clinically relevant diagnosis of sexual dysfunction (SD), is inadequately described among BCSs and represents an important research gap. Hence, the primary aim of this study was to estimate the prevalence of clinically relevant SD, in this context: impairments with associated distress, and to identify factors associated with SD among BCSs on AET. Secondly, to explore the extent of distress caused by specific impairments in sexual function. In this cross-sectional study of BCSs on adjuvant treatment with endocrine therapy for at least three months, participants completed an online survey comprising standardized measures of sexual and psychosocial function. Female Sexual Function Index (FSFI) and Sexual Complaint Screener – Women (SCS-W) were used to asses clinically relevant SD. Multiple regression analyses were performed to identify factors significantly associated with SD. In total, 333 BCSs with a mean age of 58.7 years were included in the study, of whom 227 were sexually active. Among sexually active BCSs, 134 (59%) met the criteria for having clinically relevant SD, of whom 78 (58%) perceived cancer treatment as the primary reason for their sexual problems. Factors associated with SD included vaginal dryness (adjusted OR= 2.25, 95% CI: 1.52–3.34, p p SD was highly prevalent among sexually active BCSs on AET. Sexual health is important to address independent of the woman’s age

Additional file 1 of Associations of bedtime, sleep duration, and sleep quality with semen quality in males seeking fertility treatment: a preliminary study

Additional file 1: Table S1. Association between bedtime and sleep duration with reduced semen quality

Supplementary Material for: UGT1A1*28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study

Background: Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. Objectives: To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. Methods: This is a cohort study of 1,354 very preterm infants (gestational ag